Acamprosate calcium (also referred to simply as “acamprosate”), the calcium salt of N-acetylhomotaurine, has been marketed for over 25 years as a treatment for alcoholism; specifically, it has been used to treat craving for alcohol in currently abstinent alcohol abusers. For this indication it has had limited effectiveness. Yahn S L, Watterson L R, Olive M F: Safety and efficacy of acamprosate for the treatment of alcohol dependence. Substance Abuse 7:1-12, 2013; Witkiewitz K, Saville K, Hamreus K: Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility. Therapeutics and Clinical Risk Management 8: 45-53, 2012. Despite a number of positive clinical trials, and a few negative ones, the effectiveness of the drug in actual clinical use has been relatively low. In the United States, sales of the drug have been so low that its manufacturer has stopped actively marketing it.
While the effectiveness of acamprosate calcium for alcoholism has been disappointing, 25 years of use in many countries, with over one million patients, has established that the drug is extraordinarily safe for a central nervous system (CNS) drug. Virtually no severe adverse events unequivocally attributable to the drug have been reported.
Acamprosate is remarkable not only for its safety but for its mechanism of action, which is unique among CNS drugs currently approved in the United States. It modulates glutamate and GABA transmission, diminishing the former when it is excessive and increasing the latter when it is low, but not interfering meaningfully with normal neural traffic. It does this by indirect actions including the induction of protein synthesis within cells with glutamate receptors; it does not directly bind to primary glutamate or GABA receptors sites nor is it an allosteric modulator of those sites.
Because of its actions on glutamate and GABA transmission acamprosate can correct an imbalance of excitatory (glutamate-mediated) and inhibitory (GABA-mediated) neurotransmission. Such imbalances are currently thought to play a role in causing or influencing the severity of diverse neurological and psychiatric conditions including tardive dyskinesia (TD), levodopa-induced dyskinesia (LID), Tourette Syndrome (TS), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), tinnitus, autism, generalized anxiety, depression, and addictions to alcohol, nicotine, and cocaine. Several U.S. patents (e.g., U.S. Pat. Nos. 6,057,373, 6,294,583, 6,391,922, 6,689,816, and 7,498,361; each of which is incorporated herein by reference in its entirety) describe the use of acamprosate to treat neuropsychiatric disorders, including tardive dyskinesia and other movement disorders induced by chronic exposure of patients to neuroleptic (antipsychotic) drugs, Tourette's syndrome, and mental disorders such as posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD).